Early Detection of Oral Neoplasia: Watching with New Eyes

Abstract

Yogi Berra said, "You can observe a lot just by watching." Since an estimated 47,560 new cases and 11,260 deaths from cancers of the oral cavity, oropharynx, and larynx (3% of all new cancers and 2% of all cancer deaths) occurred in the United States in 2008 (1), it is time to start "watching" these sites with new tools and insights. Despite advances in diagnostic tools and treatment modalities, overall survival rates for these cancers have improved little over the last three decades (2). The main reasons for treatment failure are second primary tumors in patients with early-stage disease (stages I and II) and local recurrence and metastases in patients with locally advanced disease (2). These cancers result from multistep carcinogenesis, which involves increasing degrees of mucosal atypia and dysplasia and molecular (epigenetic and genetic) alterations (3) and "field cancerization," in which the multistep changes occur over large areas of the carcinogen-exposed upper aerodigestive tract epithelium [the seminal field hypothesis was proposed over 50 years ago by Slaughter et al. (4) based on work in the oral cavity]. Therefore, there are three potential approaches to reduce the incidence of head and neck cancer: first, early detection and local control of high-risk focal precursor lesions; second, decrease an individual's exposure to carcinogens; and third, systemic chemopreventive agents to halt or reverse carcinogenesis in individuals exposed to a risk factor(s) and/or diagnosed with a precursor lesion (5, 6). The effect of local control by removing head and neck precursor lesions has not been established as a method of reducing cancer risk (7). Although numerous changes contribute to epithelial carcinogenesis, histologically defined intraepithelial neoplasia (IEN), or premalignant lesions, is still considered to be better than any individual molecular marker for predicting cancer risk (8, 9).Among head-and-neck cancers, oral neoplasia is particularly amenable to imaging because of the accessibility of its epithelial surface and the frequency of its routine screening by dentists. Once established for oral cancer screening, successful imaging tools could also be used in other cancers. Oral IEN initially appears as white or red patches (oral leukoplakia or erythroplakia, respectively) and carries a 17.5% risk of malignant transformation, or 36.4% in cases of dysplastic oral IEN, at 8 years (10). More precise definitions of risk are necessary; however, because carcinogenesis is multifocal and multiclonal, even within the same lesion, not all IEN progresses to cancer or can be readily detected and measured, and, at present, no specific drug can target all the causative genetic changes preceding or within IEN. To proceed with screendetected lesions and determine if excision or chemopreventive intervention is warranted, more definitive screening and riskassessment measures are required.Loss of heterozygosity profiling is one of the better current methodologies for refining the risk of progression of histologic IEN. L...

Cancer Prevention: From 1727 to Milestones of the Past 100 Years

“…New imaging approaches for IEN include optical spectroscopy (e.g., light scattering spectroscopy), chromoendoscopy (321), optical coherence tomography, and in vivo molecular imaging using activatable markers (322). Recent advances in autofluorescence with probability mapping should provide a more reliable screen for detecting oral neoplasia (323).…”

Effects of Oral Contraceptives or a Gonadotropin-Releasing Hormone Agonist on Ovarian Carcinogenesis in Genetically Engineered Mice

“…Such studies will need feasible, effective means for detecting true prevention endpoints, such as time to tumor development, for which small-animal imaging techniques such as ultrasound and MRI show promise. Advances in molecular imaging, including the ability to detect enzyme activity and follow the effect of molecular alterations in tissue in real time (41, 42), will further improve our understanding of chemopreventive studies in animals.…”

Proliferative Verrucous Leukoplakia (PVL)

“…These tests should be performed in a prospective, collaborative, and multicenter setting. [43][44][45] TREATMENT Currently, no curative treatment exists for PVL or multifocal conventional leukoplakia with dysplasia. Preinvasive disease is best managed with less aggressive modalities, such as CO 2 laser ablation or photodynamic therapy.…”